2,2-双(氟甲基)-6-(三氟甲基)-2H-1-苯并吡喃-4-羧酸 | 152661-72-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 中文名称: 2,2-双(氟甲基)-6-(三氟甲基)-2H-1-苯并吡喃-4-羧酸
• 英文名称: 2,2-bis(fluoromethyl)-6-(trifluoromethyl)-2H-1-benzopyran-4-carboxylic acid
• 英文别名: 2,2-bis(fluoromethyl)-6-trifluoromethyl-2H-1-benzopyran-4-carboxylic acid；2,2-bis(fluoromethyl)-6-(trifluoromethyl)chromene-4-carboxylic acid
• CAS: 152661-72-8
• 化学式: C₁₃H₉F₅O₃
• 分子量: 308.205
• InChiKey: UNXJQBYPFPFIKT-UHFFFAOYSA-N

物化性质

• 沸点：
  371.8±42.0 °C(Predicted)
• 密度：
  1.428±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2,2-双(氟甲基)-6-(三氟甲基)-2H-1-苯并吡喃-4-羧酸 在 劳森试剂 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 1,2-二氯乙烷 为溶剂， 反应 14.0h， 生成 N-(2-Cyanoethyl)-2,2-bis(fluoromethyl)-6-trifluoromethyl-2H-1-benzopyran-4-carbothioamide
  参考文献：
  名称：

  6-Substituted 2,2-Bis(fluoromethyl)-benzopyran-4-carboxamide K + channel openers

  摘要：

  In the course of our study to find an ideal antihypertensive potassium channel opener (KCO), N-(2-cyanoethyl)-2,2 bis(fluoromethyl)-6-pentafluoroethyl-2H-1-benzopyran-4-carboxamide (13f, KC-515) showed a highly potent, slow and long-lasting antihypertensive effect with reduced reflex tachycardia, together with the beneficial effects of KCO such as improvement in lipid metabolism. These profiles identify KC-515 as a potential candidate. In conscious spontaneously hypertensive rats (SHR), the onset of the hypotensive effect of KC-515 (13f) was gradual and the maximum response was attained at around 6 h after dosing. The duration of action was over 18 h for 0.1 mg/kg. When administered to Zucker rats for 2 weeks with 0.03-0.3 mg/kg po range in the antihypertensive doses in hypertensive rat models, KC-515 (13f) significantly and dose-dependently reduced serum triglycerides to less than 70% of control without affecting total cholesterol. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00064-x
• 作为产物：
  描述：

  2,2-bis(fluoromethyl)-6-iodo-2H-1-benzopyran-4-carboxylic acid ethyl ester 在 盐酸 、 氢氧化钾 、 碘化亚铜 作用下， 以 (2S)-N-methyl-1-phenylpropan-2-amine hydrate 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 2,2-双(氟甲基)-6-(三氟甲基)-2H-1-苯并吡喃-4-羧酸
  参考文献：
  名称：

  N-(2-cyanoethyl)-6-fluoroalkyl-2h-1-benzopyran derivatives

  摘要：

  本文描述了由以下公式表示的苯并吡喃衍生物：##STR1## 其中R、X和Y代表以下任意组合之一： ______________________________________ R X Y ______________________________________ C.sub.2 F.sub.5 O H C.sub.2 F.sub.5 S H CF.sub.3 S F C.sub.2 F.sub.5 S F C.sub.3 F.sub.7 S F ______________________________________ PAL及其药学上可接受的盐。这些化合物具有优异的钾通道活性，并且从安全性方面也表现出色。

  公开号：

  US05646310A1

文献信息

• Remedies for peripheral circulation disturbances
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：US06248777B1

  公开（公告）日：2001-06-19

  It is an object of the present invention to provide novel therapeutic agents for peripheral vascular disease. The present invention provides pharmaceutical compositions comprising a benzopyran or benzoxazine derivative of the general formula (1): wherein; R1 represents a hydrogen atom, a lower alkyl group or an aryl group, or R1 directly couples with Q or R11 to form a single bond; R2represents a substituted or unsubstituted amino group, a saturated or unsaturated heterocyclic group, A—O—or —C(═X)Y; Q represents ═N—, N+—O−or C(R11)R12; R3 and R4 each represent a hydrogen atom, a lower alkyl group or a substituted lower alkyl group having a halogen atom or a lower alkoxy group as a substituent or the like; and R5 and R6 each represent a hydrogen atom, a halogen atom, a lower alkyl group, a lower haloalkyl group or the like; and a pharmaceutically acceptable carrier.

  本发明的目的是为外周血管疾病提供新型治疗药物。 本发明提供了包含一种通式（1）的苯并吡喃或苯并噁嗪衍生物的药物组合物： 其中； R1代表氢原子、较低的烷基或芳基，或R1直接与Q或R11结合形成单键； R2代表取代或未取代的氨基、饱和或不饱和的杂环基、A—O—或—C(═X)Y； Q代表═N—、N+—O−或C(R11)R12； R3和R4各自代表氢原子、较低的烷基或具有卤原子或较低的烷氧基等取代基的取代的较低烷基，R5和R6各自代表氢原子、卤原子、较低的烷基、较低的卤代烷基或类似物；以及一种药学上可接受的载体。
• Benzopyran derivatives
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：US05646308A1

  公开（公告）日：1997-07-08

  Benzopyran derivatives represented by formula (I): ##STR1## wherein X represents .dbd.O, .dbd.S, .dbd.N--Z, etc. (Z represents a lower alkyl group, etc.); Y represents a substituted amino group, an alkoxy group, an alkylthio group, etc., and R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 each represents a hydrogen atom, a lower alkyl group, etc, are disclosed. The benzopyran derivative exhibit K.sup.+ channel opening activities and are widely applicable as antiasthmatics, antiepileptics, and the like.

  公式（I）所代表的苯并吡喃衍生物：其中X代表.dbd.O，.dbd.S，.dbd.N--Z等（Z代表较低的烷基基团等）；Y代表取代氨基团，烷氧基团，烷基硫基团等；R.sub.1，R.sub.2，R.sub.3，R.sub.4和R.sub.5分别代表氢原子，较低的烷基基团等。这些苯并吡喃衍生物表现出K.sup.+通道开放活性，并广泛应用于抗哮喘药物，抗癫痫药物等。
• Process for producing 4-substituted benzopyran derivatives
  申请人：Central Glass Company, Limited

  公开号：US20030109574A1

  公开（公告）日：2003-06-12

  The present invention relates to a first process for producing a 2,2-bis(fluoromethyl)-6-(perfluoroalkyl)-2H-1-benzopyran-4-carboxylic acid. The first process includes the steps of (a) reacting a 2,2-bis(fluoromethyl)-6-(perfluoroalkyl)-2H-1-benzopyran-4-one with a perfluoroalkanesulfonic acid anhydride in the presence of a base, thereby obtaining a perfluoroalkanesulfonic 2,2-bis(fluoromethyl)-6-(perfluoroalkyl)-2H-1-benzopyran-4-yl ester; and (b) reacting the benzopyranyl ester with carbon monoxide in the presence of a palladium complex compound and a base, thereby obtaining the carboxylic acid. The present invention further relates to a second process for producing a 2-hydroxy-5-(perfluoroalkyl)acetophenone, which can be a raw material for producing the carboxylic acid. The second process includes the steps of (c) reacting a 4-(perfluoroalkyl)alkoxybenzene with acetic anhydride or an acyl halide in the presence of a Lewis acid, thereby obtaining a 2-alkoxy-5-(perfluoroalkyl)acetophenone; and (d) dealkylating the 2-alkoxy-5-(perfluoroalkyl)acetophenone by a dealkylating agent.

  本发明涉及一种用于生产2,2-双(氟甲基)-6-(全氟烷基)-2H-1-苯并吡喃-4-羧酸的第一方法。该第一方法包括以下步骤：(a)在碱的存在下，将2,2-双(氟甲基)-6-(全氟烷基)-2H-1-苯并吡喃-4-酮与全氟烷基磺酸酐反应，从而获得全氟烷基磺酸酯化的2,2-双(氟甲基)-6-(全氟烷基)-2H-1-苯并吡喃-4-基酯；(b)在钯络合物和碱的存在下，将苯并吡啶酯与一氧化碳反应，从而获得羧酸。本发明还涉及一种用于生产2-羟基-5-(全氟烷基)苯乙酮的第二方法，该化合物可用作生产羧酸的原料。该第二方法包括以下步骤：(c)在Lewis酸的存在下，将4-(全氟烷基)烷氧基苯与乙酸酐或酰卤反应，从而获得2-烷氧基-5-(全氟烷基)苯乙酮；(d)通过脱烷基试剂脱烷基化2-烷氧基-5-(全氟烷基)苯乙酮。
• Processes for the preparation of 4-substituted benzopyran derivatives
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：US06455708B1

  公开（公告）日：2002-09-24

  Starting, for example, from 1-fluoro-2-fluoromethyl-3-butyn-2-yl 4-trifluoromethylphenyl; ether, N-(2-cyanoethyl)-5-fluoro-4-fluoromethyl-4-(4-trifluoromethylphenoxy)-2-pentynamide is produced and then cyclized to synthesize 2,2-bis(fluoromethyl)-N-(2-cyanoethyl)-6-trifluoromethyl-2H-1-benzopyran-4-carboxamide. The invention processes for producing 4-substituted benzopyran derivatives involve fewer steps, feature greater safety and allow for easier purification than the prior art processes.

  例如，从1-氟-2-氟甲基-3-丁炔-2-基-4-三氟甲基苯基醚开始；产生N-(2-氰乙基)-5-氟-4-氟甲基-4-(4-三氟甲基苯氧基)-2-戊炔酰胺，然后环化合成2,2-双(氟甲基)-N-(2-氰乙基)-6-三氟甲基-2H-1-苯并吡喃-4-甲酰胺。本发明的生产4-取代苯并吡喃衍生物的工艺步骤比现有技术的工艺步骤更少，具有更高的安全性，并且比以往更容易纯化。
• Processes for producing 4-substituted benzopyran derivatives
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：US20030065189A1

  公开（公告）日：2003-04-03

  Starting, for example, from 1-fluoro-2-fluoromethyl-3-butyn-2-yl 4-trifluoromethylphenyl ether, N-(2-cyanoethyl)-5-fluoro-4-fluoromethyl-4-(4-trifluoromethylphenoxy)-2-pentynamide is produced and then cyclized to synthesize 2,2-bis(fluoromethyl)-N-(2-cyanoethyl)-6-trifluoromethyl-2H-1-benzopyran-4-carboxamide. The invention processes for producing 4-substituted benzopyran derivatives involve fewer steps, feature greater safety and allow for easier purification than the prior art processes.

  以1-氟-2-氟甲基-3-丁炔-2-基-4-三氟甲基苯醚为起始物，生产N-(2-氰基乙基)-5-氟-4-氟甲基-4-(4-三氟甲基苯氧基)-2-戊炔酰胺，然后环化合成2,2-双(氟甲基)-N-(2-氰基乙基)-6-三氟甲基-2H-1-苯并吡喃-4-羧酰胺。该发明生产4-取代苯并吡喃衍生物的工艺步骤较少，更安全，并且易于纯化，比现有技术工艺更具优势。